1. Human MYC G-quadruplex: From discovery to a cancer therapeutic target.
- Author
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Wang W, Hu S, Gu Y, Yan Y, Stovall DB, Li D, and Sui G
- Subjects
- Binding Sites, G-Quadruplexes drug effects, Gene Expression Regulation, Neoplastic, Humans, Ligands, Neoplasms drug therapy, Promoter Regions, Genetic drug effects, Proto-Oncogene Proteins c-myc metabolism, Small Molecule Libraries therapeutic use, Up-Regulation, Neoplasms genetics, Proto-Oncogene Proteins c-myc chemistry, Proto-Oncogene Proteins c-myc genetics, Small Molecule Libraries pharmacology
- Abstract
Overexpression of the MYC oncogene is a molecular hallmark of both cancer initiation and progression. Targeting MYC is a logical and effective cancer therapeutic strategy. A special DNA secondary structure, the G-quadruplex (G4), is formed within the nuclease hypersensitivity element III
1 (NHE III1 ) region, located upstream of the MYC gene's P1 promoter that drives the majority of its transcription. Targeting such G4 structures has been a focus of anticancer therapies in recent decades. Thus, a comprehensive review of the MYC G4 structure and its role as a potential therapeutic target is timely. In this review, we first outline the discovery of the MYC G4 structure and evidence of its formation in vitro and in cells. Then, we describe the functional role of G4 in regulating MYC gene expression. We also summarize three types of MYC G4-interacting proteins that can promote, stabilize and unwind G4 structures. Finally, we discuss G4-binding molecules and the anticancer activities of G4-stabilizing ligands, including small molecular compounds and peptides, and assess their potential as novel anticancer therapeutics., (Copyright © 2020 Elsevier B.V. All rights reserved.)- Published
- 2020
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